No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis.

STUDY QUESTION: What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)? SUMMARY ANSWER: The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone. WHAT IS KNOWN ALREADY: Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer. STUDY DESIGN, SIZE, DURATION: This IPD MA included all existing RCTs (n = 4) in which embryo selection by morphology was compared with embryo selection by morphology and the use of NIR spectroscopy of spent embryo culture medium by the Viametrics-E(™). PARTICIPANTS/MATERIALS, SETTING, METHODS: Searches of PubMed, the Cochrane Library and the WHO International Clinical Trials Registry were conducted and the sole manufacturer of the Viametrics-E(™) was consulted to identify clinics where an RCT comparing embryo selection by morphology to embryo selection by morphology and the use of the Viametrics-E(™) (NIR viability score) was performed. A total of 20 citations were potentially eligible for inclusion, two of which met the inclusion criteria. The manufacturer of the Viametrics-E(™) provided two additional clinical sites of use. In total, four RCTs were identified as eligible for inclusion. The IPD MA was based on a fixed effect model due to the lack of heterogeneity between included studies. Differences between study groups were tested and reported using logistic regression models adjusted for significant confounders. The pooled analysis of the primary outcome led to a total sample size of 924 patients: 484 patients in the control group (embryo selection by morphology alone) and 440 patients in the treatment group (embryo selection by morphology plus NIR spectroscopy). MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates in the control group and the NIR group were 34.7% (168 of 484) and 33.2% (146 of 440), respectively. The pooled odds ratio (OR) was 0.98 [95% confidence interval (CI) 0.74-1.29], indicating no difference in live birth rates between the two study groups. The data of the four studies showed no significant heterogeneity (I(2) = 26.2% P = 0.26). The multivariate regression analysis including all confounders show that maternal age (OR 0.90, 95% CI 0.87-0.94) and the number of previous IVF cycles (OR 0.83, 95% CI 0.71-0.96) were significantly related to live birth. The study group (i.e. embryo selection by morphology or embryo selection by morphology plus NIR) was not related to live birth (OR 0.97, 95% CI 0.73-1.29). LIMITATIONS AND REASONS FOR CAUTION: The availability of at least two similar best quality embryos as an inclusion criterion prior to transfer in the two largest RCTs might have caused a selection bias towards a better prognosis patient group. WIDER IMPLICATIONS OF THE FINDINGS: There is at present no evidence that NIR spectroscopy of spent embryo culture media in its current form can be used in daily practice to improve live birth rates.

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial.

BACKGROUND: Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers. METHODS: We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6-7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation. RESULTS: The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was -0.8% (95% confidence interval -11.4 to 10.2). CONCLUSIONS: This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability. CLINICAL TRIALS IDENTIFIER: ISRCTN23817363.

Re-analysis of 166 embryos not transferred after PGS with advanced reproductive maternal age as indication.

BACKGROUND: In a randomized controlled study aiming to test the effectiveness of preimplantation genetic screening (PGS) in women of advanced maternal age, embryos diagnosed as chromosomally abnormal and those with no diagnosis were fixed for reanalysis. The aim of this study was to determine how well the chromosomal constitution of one biopsied blastomere reflects the status of the entire embryo. METHODS: One hundred and seventy-three embryos diagnosed as chromosomally abnormal, 22 with no PGS result and four degenerated embryos originally diagnosed as normal were fixed and reanalysed by fluorescence in situ hybridization. RESULTS: In total, 199 embryos were fixed, of which 166 were successfully reanalysed. One hundred and sixty embryos were found to be chromosomally abnormal; 48 of the reanalysed embryos with an initial diagnosis (149) had at least one cell with exactly the same chromosomal constitution shown in the first PGS analysis (34.2%). The reanalysis confirmed the initial overall chromosomally abnormal status of the embryo in 95.9% of the cases. Of all chromosomally abnormal embryos, 4.1% were diagnosed as false positive. The risk for false negative rate was at least 4.1%. CONCLUSIONS: PGS seems to be a good method for selecting against chromosomally abnormal embryos but not for determining an embryo's exact chromosomal constitution.

Comparison between a conventional index of progressive sperm motility and movement variables analysed by CellSoft.

Two different techniques of human sperm motion analysis were compared. In 25 ejaculates, diluted to an appropriate concentration, the sperm motion index called "specific progressive motility" (SPM) was assessed by a modified conventional method. The same sperm preparations were also analysed by the CellSoft system for computer assisted sperm analysis (CASA). The SPM-value was found to correspond mainly to the variables motility and curvilinear velocity presented by CASA (multiple r = 0.92, P less than 0.001). Linearity of sperm progression, lateral head displacement, and beat cross frequency did not significantly contribute to the relationship between SPM and CASA. For comparative studies between SPM and CASA the logarithmic values of SPM are recommended.

Effects of propranolol and caffeine on movement characteristics of human sperm.

Human sperm, separated on Percoll gradients and transferred to cell culture medium, were exposed to various concentrations of propranolol (0.8-800 microM) or caffeine (3 microM-17 mM) for 4 h. Their motility pattern was analysed after 5 min and 4 h, employing the computerized Cellsoft system. Curvilinear velocity (VCL), percentage motile sperm, linearity (LIN), mean amplitude of lateral head displacement (ALHMEAN) and beat cross-frequency (BCF) were assessed. Both drugs had a practically immediate effect on the sperm. Propranolol concentrations greater than 80 microM had a negative effect on all movement variables, except VCL and ALHMEAN, which showed a slight, non-significant, initial increase. LIN and the percentage motile sperm appeared to be somewhat negatively affected at lower concentrations (80 microM) than the other variables, and were reduced further at higher concentrations and with time. The presence of 800 microM propranolol immobilized all sperm within 4 h. Caffeine at 1.7 and 5 mM, increased VCL and ALHMEAN. In contrast, the highest caffeine concentration tested (17 mM) had a negative effect on all variables at 4 h after addition.